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Parnham, M.J. (author), Bogaards, J.J.P. (author), Schrander, F. (author), Schut, M.W. (author), Orešković, K. (author), Mildner, B. (author), TNO Kwaliteit van Leven (author)
PLD-118 is a novel, oral antifungal drug, under development for the treatment of Candida infections. Possible metabolism of PLD-118 by rat, dog and human S9 liver homogenates and inhibition of human cytochrome P450 (CYP) enzymes were investigated. PLD-118 (10 and 100 μm) incubated for 0-60 min with S9 fractions and NADPH was determined by HPLC,...
article 2005
document
Smokovitis, A. (author), Astrup, T. (author), Gaubius instituut TNO (author)
Fibrinolytic activity (caused by a plasminogen activator) in the spinal cord was highest in the rat, lowest in the rabbit, and intermediate in the guinea pig. In all species the activity was highest in relation to the pia mater. The central spinal canal was active in the rat and the rabbit, but mostly inactive in the guinea pig. Foci of activity...
article 1978
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Padro, T. (author), Quax, P.H.A. (author), van den Hoogen, C.M. (author), Roholl, P. (author), Verheijen, J.H. (author), Emeis, J.J. (author), Gaubius Instituut TNO (author)
Plasminogen activator (PA) and PA inhibitor (PAI) antigen, activity, and mRNA were analyzed in the three layers of rat aorta, and the effect of endotoxin on PA and PAI was studied. All PA activity in aorta was identified as tissue-type PA (TPA) activity; no urokinase-type PA was detected. In the tunica adventitia TPA activity, TPA antigen, and...
article 1994
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Kienhuis, A.S. (author), Wortelboer, H.M. (author), Hoflack, J.C. (author), Moonen, E.J. (author), Kleinjans, J.C.S. (author), van Ommen, B. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)
Sandwich-cultured primary rat hepatocytes are often used as an in vitro model in toxicology and pharmacology. However, loss of liver-specific functions, in particular, the decline of cytochrome P450 (P450) enzyme activity, limits the value of this model for prediction of in vivo toxicity. In this study, we investigated whether a hepatic in vitro...
article 2006
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van Raaij, J.A.G.M. (author), Kaptein, E. (author), Visser, T.J. (author), van den Berg, K.J. (author), Medisch Biologisch Laboratorium TNO (author)
Metabolism of thyroid hormones was investigated in WAG/MBL rats that had been exposed to hexachlorobenzene (HCB). Serum thyroxine (T4) levels were lowered by 35.5%, whereas triiodothyronine (T3) levels were not changed. Bile flow, as well as T4 excretion in bile were increased by HCB treatment. Analysis of bile by HPLC revealed a more than 3...
article 1993
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Maas, W.J.M. (author), Leeman, W.R. (author), Groten, J.P. (author), van de Sandt, J.J.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
Precision-cut liver slices are frequently used to study hepatic toxicity and metabolism of xenobiotics in vitro. Successful cryopreservation techniques will enhance an efficient and economic use of scarcely available (human) liver tissue. For primary hepatocytes, slow freezing has been accepted as the best approach towards successful...
article 2000
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Ladics, G.S. (author), Holsapple, M.P. (author), Astwood, J.D. (author), Kimber, I. (author), Knippels, L.M.J. (author), Helm, R.M. (author), Dong, W. (author)
There is a need to assess the safety of foods deriving from genetically modified (GM) crops, including the allergenic potential of novel gene products. Presently, there is no single in vitro or in vivo model that has been validated for the identification or characterization of potential food allergens. Instead, the evaluation focuses on risk...
article 2003
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Jaspers, R.M.A. (author), Muijser, H. (author), Lammers, J.H.C.M. (author), Kulig, B.M. (author), Medisch Biologisch Laboratorium TNO Centraal Instituut voor Voedingsonderzoek TNO (author)
Modification of auditory evoked startle responding using prepulse inhibition was used to examine the effects of trichloroethylene (TCE) exposure on auditory thresholds. Rats were exposed by inhalation to 0, 1500, or 3000 ppm TCE for 18 hours per day, 5 days a week for 3 weeks. Auditory thresholds for 5 and 20 kHz tones were measured before...
article 1993
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Kitayama, K. (author), Nakai, D. (author), Kono, K. (author), van der Hoop, A.G. (author), Kurata, H. (author), de Wit, E.C. (author), Cohen, L.H. (author), Inaba, T. (author), Kohama, T. (author), TNO Preventie en Gezondheid (author)
1-{7-[(1-(3,5-Diethoxyphenyl)-3-{[(3,5-difluorophenyl)(ethyl)amino]carbo nyl}-4-oxo-1,4-dihydroquinolin-7-yl)oxy]heptyl}-1-methylpiperidinium bromide, R-146224, is a potent, specific ileum apical sodium-dependent bile acid transporter (ASBT) inhibitor; concentrations required for 50% inhibition of [3H]taurocholate uptake in human ASBT-expressing...
article 2006
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Damsten, M.C. (author), Commandeur, J.N.M. (author), Fidder, A. (author), Hulst, A.G. (author), Touw, D. (author), Noort, D. (author), Vermeulen, N.P.E. (author), TNO Defensie en Veiligheid (author)
Covalent binding of reactive electrophilic intermediates to proteins is considered to play an important role in the processes leading to adverse drug reactions and idiosyncratic drug reactions. Consequently, both for the discovery and the development of new drugs, there is a great interest in sensitive methodologies that enable the detection of...
article 2007
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Rijnkels, J.M. (author), Hollanders, V.M.H. (author), Woutersen, R.A. (author), Koeman, J.H. (author), Alink, G.M. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
The potential inhibitory effects of a vegetables-fruit mixture on the initiation and promotion phases of azoxymethane-induced colorectal carcinogenesis were examined in rats fed low- or high-fat diets. Rats were fed low-fat diets (20 energy percent, Diets A and B) or high-fat diets (40 energy percent, Diets C and D), supplemented with a...
article 1998
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Anderson, D. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO BIBRA (author)
Butadiene (BD) and its 2-methyl analogue, isoprene, have been extensively studied in animals and BD in population studies. Both chemicals are metabolised by liver cytochrome P450 dependent monogenases to monoepoxide and diepoxide intermediates. The diepoxide intermediates of both compounds were mutagenic in Salmonella typhimurium. However,...
article 2001
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Lina, B.A.R. (author), Bos-Kuijpers, M.H.M. (author), Til, H.P. (author), Bär, A. (author)
The potential toxicity and carcinogenicity of erythritol, a low-calorie sugar substitute, were examined in Wistar Crl:(WI) WU BR rats. Groups of 50 rats of each sex consumed diets with 0, 2, 5, or 10% erythritol, or 10% mannitol, for a period of 104-107 weeks. To each of these main groups, two satellite groups of 20 males each were attached for...
article 1996
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Hissink, A.M. (author), Krüse, J. (author), Kulig, B.M. (author), Verwei, M. (author), Muijser, H. (author), Salmon, F. (author), Leenheers, L.H. (author), Owen, D.E. (author), Lammers, J.H.C.M. (author), Freidig, A.P. (author), McKee, R.H. (author), TNO Kwaliteit van Leven (author)
As part of a project designed to develop a framework for extrapolating acute central nervous system (CNS) effects of hydrocarbon solvents in animals to humans, experimental studies were conducted in rats and human volunteers in which acute CNS effects were measured and toxicokinetic data were collected. A complex hydrocarbon solvent, white...
article 2007
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Izeboud, C.A. (author), Hoebe, K.H.N. (author), Grootendorst, A.F. (author), Nijmeijer, S.M. (author), van Miert, A.S. (author), Witkamp, R.F. (author), Rodenburg, R.J.T. (author), TNO Voeding (author)
Objective and Design: To investigate the effects of β2- adrenoceptor (β2-AR) stimulation on endotoxin-induced liver damage and systemic cytokine levels in rats. Subjects: Standard male Wistar rats. Treatment: A disease-model of lipolysaccharide (LPS)-induced acute systemic inflammation was used. The β2-selective AR agonist clenbuterol was...
article 2004
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Kuper, C.F. (author), van Zijverden, M. (author), Klaassen, C. (author), Tegelenbosch-Schouten, M. (author), Wolterbeek, A.P.M. (author), TNO Kwaliteit van Leven (author)
The effects of cyclosporin A (CY) and cyclophosphamide (CPS) on Peyer's patches (PP) were studied in Wistar rats, exposed in utero and neonatally or during adult age. In one study, pregnant dams received 5 or 15 mg/kg bw/day CY from gestation day 6 to day 21 of lactation. In two other studies, animals were exposed at young adult age: female rats...
article 2007
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Broerse, J.J. (author), Radiobiologisch Instituut TNO (author)
Values of the relative biological effectiveness (RBE) of fast neutrons for effect on normal tissue depend not only on the neutron energy and the dose, but also on the type of tissue irradiated. Values of the RBE of 15 MeV neutrons are reviewed for rapidly proliferating rodent tissue, such as mouse bone marrow, mouse intestine and rat skin...
article 1974
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Cassee, F.R. (author), Muijser, H. (author), Duistermaat, E. (author), Freijer, J.J. (author), Geerse, E.K.B. (author), Marijnissen, J.C.M. (author), Arts, J.H.E. (author), Instituut CIVO-Toxicologie en Voeding TNO (author)
The relative importance of the three particulate matter (PM) size fractions in ambient air, i.e. coarse (2.5-10 μm), fine (0.1-2.5 μm) and ultrafine (< 0.1 μm) fractions, on the induction of adverse health effects is still unknown. Moreover, there is no straightforward relationship between ambient concentration levels, exposure (external dose)...
article 2002
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Padró, T. (author), van den Hoogen, C.M. (author), Emeis, J.J. (author), Instituut voor verouderings- en vaatziekten onderzoek TNO (author)
The aim of the present study was to investigate whether hypothyroidism would affect the components of the rat plasma fibrinolytic system. Hypothyroidism was induced by feeding rats a thiouracil-containing diet for 2 weeks. During this period, half of the animals received subcutaneous injections of L-thyroxine (20 μg/kg daily) to restore thyroid...
article 1993
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Zwart, A. (author), Arts, J.H.E. (author), ten Berge, W.F. (author), Appelman, L.M. (author)
A new design for acute inhalation toxicity testing was evaluated and compared with results obtained according to OECD guideline 403. The new design consists of a range-finding test, which is compatible with a conventional limit test, and can be followed by determination of a concentration-time-mortality relationship, enabling calculation of LC50...
article 1992
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